4 years ago

Tpl2 promotes innate cell recruitment and effector T cell differentiation to limit Citrobacter rodentium burden and dissemination.

Latha K, Li X, Nagy T, Watford WT, Acuff NV
Tumor progression locus 2 (Tpl2) is a serine-threonine kinase that regulates Th1 differentiation, secretion of the inflammatory cytokine IFNγ, and host defense against the intracellular pathogens Toxoplasma gondii, Listeria monocytogenes, and Mycobacterium tuberculosis However, there is relatively little known about the contribution of Tpl2 to Th17 differentiation and immune cell function during infection with an extracellular pathogen. The goal of this study was to determine whether Tpl2 influences the immune response generated to the extracellular bacterium Citrobacter rodentium, which induces a mixed Th1/Th17 response. During peak infection with C. rodentium, Tpl2-/- mice experienced greater bacterial burdens with evidence of dissemination to the liver and spleen but ultimately cleared the bacteria within three weeks post infection similar to wild type mice. Tpl2-/- mice also recruited fewer neutrophils and monocytes to the colon during peak infection, which correlated with increased bacterial burdens. In mixed bone marrow chimeras, Tpl2 was shown to play a T-cell intrinsic role in promoting both IFNγ and IL-17A production during infection with C. rodentium However, upon CD4 T cell transfer into Rag-/- mice, Tpl2-/- CD4 T cells were equally protective as wild type CD4 T cells against dissemination of bacteria and mortality. These data indicate that enhanced bacterial burdens in Tpl2-/- mice are not caused primarily by impairments in CD4 T cell function but result from defects in innate immune cell recruitment and function.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28760932

DOI: PubMed:28760932

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